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A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

Primary Purpose

Pneumonia, Pneumocystis Carinii, HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atovaquone
Sulfamethoxazole-Trimethoprim
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia, Pneumocystis Carinii focused on measuring Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Naphthoquinones, Antifungal Agents, Acquired Immunodeficiency Syndrome, Sulfamethoxazole-Trimethoprim

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Patient must have the following: Presumptive diagnosis of AIDS as defined by the CDC. Untreated Pneumocystis carinii pneumonia (PCP). Willingness and ability to give informed consent. Prior Medication: Allowed: Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Judged by the investigator to be in impending respiratory failure. Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy. Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult. Concurrent Medication: Excluded: Corticosteroid treatment (except replacement therapy or patients in Group B). Ganciclovir. Zidovudine (AZT). Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.). Drugs likely to have anti-pneumocystis effect such as: Sulfonamides. Pentamidine. Dapsone. Trimethoprim. Other DHFR inhibitors. Primaquine. Clindamycin. Sulfonylureas. Patients with the following are excluded: Judged by the investigator to be in impending respiratory failure. Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP. Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period. Unable to take medication orally or unwilling or unable to take study medication with food. Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol. Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome. Prior Medication: Excluded: Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP. Blood transfusions.

Sites / Locations

  • Univ of Alabama at Birmingham
  • Kaiser Foundation Hosp
  • USC
  • Dr Richard Meyer
  • UCLA CARE Ctr
  • Infectious Disease Med Group
  • Univ of California / San Diego Treatment Ctr
  • San Francisco Gen Hosp
  • UCSF - San Francisco Gen Hosp
  • Dr Marcus Conant
  • Georgetown Univ Med Ctr
  • Veterans Administration Med Ctr
  • Dr Winkler Weinberg
  • Johns Hopkins Univ School of Medicine
  • Natl Inst of Allergy & Infect Dis / Cln Ctr
  • Washington Univ School of Medicine
  • Beth Israel Med Ctr / Peter Krueger Clinic
  • Saint Vincent's Hosp and Med Ctr
  • Harlem AIDS Treatment Group / Harlem Hosp Ctr
  • Duke Univ Med Ctr
  • Univ of Cincinnati
  • Good Samaritan Hosp
  • Buckley Braffman Stern Med Associates
  • Regional Med Ctr at Memphis
  • The Regional Medical Ctr, Memphis
  • Plaza Med Ctr
  • Baylor College of Medicine
  • CHU Saint Pierre
  • Dr Julio S G Montaner
  • Wellesley Hosp
  • Montreal Gen Hosp
  • Hopital Bichat - Claude Bernard
  • August-Viktoria-Krankenhaus Chefarst derII Inneren Abteilung
  • Universitat Munchen / Medizinische Poliklinik
  • Natac Med Centre
  • San Juan Veterans Administration Med Ctr
  • Kobler Centre / Saint Stephen's Hosp
  • Saint Mary's Hosp

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
February 25, 2011
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000655
Brief Title
A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
Official Title
A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
January 1992 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP. Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
Detailed Description
Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients. Patients are randomized into one of two treatment groups to receive either (1) 566C80 for 21 days, or (2) SMX/TMP for 21 days. Patients will be stratified according to severity of PCP. Group A will be those with an arterial-alveolar (A-a) DO2 < 35 mm Hg. Group B will have an A-a DO2 of 35-45 mm Hg., and will also be required to receive therapy with Corticosteroids. All doses are taken with food. During the 21 days of treatment, patients are examined clinically for adverse effects and have hematology (blood-related) and clinical chemistry studies conducted a minimum of 2 times weekly. More frequent monitoring may be required at the discretion of the investigator. To evaluate the effectiveness of study medication, the clinical status of each patient is evaluated 2 to 3 times per week (e.g., dyspnea score, cough score, chest tightness/pain score, vital signs). Also, on days 7 and 21 of treatment, an arterial blood gas measurement and chest X-ray are performed. Patients who experience severe toxicities will be discontinued from the study and placed on alternative therapy. Patients will also be removed from study if they show significant clinical deterioration within the first 7 days of therapy or if there is no improvement after 10 days of therapy. This study involves a double placebo with one group randomized to receive oral 566C80 and placebo tablets which look like SMX/TMP while the other group will receive SMX/TMP and placebo tablets looking like 566C80.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Pneumocystis Carinii, HIV Infections
Keywords
Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Naphthoquinones, Antifungal Agents, Acquired Immunodeficiency Syndrome, Sulfamethoxazole-Trimethoprim

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Enrollment
300 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Atovaquone
Intervention Type
Drug
Intervention Name(s)
Sulfamethoxazole-Trimethoprim

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patient must have the following: Presumptive diagnosis of AIDS as defined by the CDC. Untreated Pneumocystis carinii pneumonia (PCP). Willingness and ability to give informed consent. Prior Medication: Allowed: Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Judged by the investigator to be in impending respiratory failure. Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy. Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult. Concurrent Medication: Excluded: Corticosteroid treatment (except replacement therapy or patients in Group B). Ganciclovir. Zidovudine (AZT). Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.). Drugs likely to have anti-pneumocystis effect such as: Sulfonamides. Pentamidine. Dapsone. Trimethoprim. Other DHFR inhibitors. Primaquine. Clindamycin. Sulfonylureas. Patients with the following are excluded: Judged by the investigator to be in impending respiratory failure. Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP. Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period. Unable to take medication orally or unwilling or unable to take study medication with food. Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol. Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome. Prior Medication: Excluded: Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP. Blood transfusions.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hughes WT
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Kaiser Foundation Hosp
City
Harbor City
State/Province
California
ZIP/Postal Code
90710
Country
United States
Facility Name
USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Dr Richard Meyer
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
UCLA CARE Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Infectious Disease Med Group
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Univ of California / San Diego Treatment Ctr
City
San Diego
State/Province
California
ZIP/Postal Code
921036325
Country
United States
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
UCSF - San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Dr Marcus Conant
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Georgetown Univ Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Veterans Administration Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
Dr Winkler Weinberg
City
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
Johns Hopkins Univ School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Natl Inst of Allergy & Infect Dis / Cln Ctr
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Washington Univ School of Medicine
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
Beth Israel Med Ctr / Peter Krueger Clinic
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Saint Vincent's Hosp and Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Harlem AIDS Treatment Group / Harlem Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Univ of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Good Samaritan Hosp
City
Portland
State/Province
Oregon
ZIP/Postal Code
972103079
Country
United States
Facility Name
Buckley Braffman Stern Med Associates
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Regional Med Ctr at Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
The Regional Medical Ctr, Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Plaza Med Ctr
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
CHU Saint Pierre
City
Brussels
Country
Belgium
Facility Name
Dr Julio S G Montaner
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Wellesley Hosp
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Montreal Gen Hosp
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Hopital Bichat - Claude Bernard
City
Paris
Country
France
Facility Name
August-Viktoria-Krankenhaus Chefarst derII Inneren Abteilung
City
Berlin 41
Country
Germany
Facility Name
Universitat Munchen / Medizinische Poliklinik
City
Munich 2
Country
Germany
Facility Name
Natac Med Centre
City
Amsterdam
Country
Netherlands
Facility Name
San Juan Veterans Administration Med Ctr
City
San Juan
ZIP/Postal Code
009275800
Country
Puerto Rico
Facility Name
Kobler Centre / Saint Stephen's Hosp
City
London
Country
United Kingdom
Facility Name
Saint Mary's Hosp
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
Citation
Hughes W, et al. Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration. Int Conf AIDS. 1992 Jul 19-24;8(1):We48 (abstract no WeB 1019)
Results Reference
background
PubMed Identifier
8479489
Citation
Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993 May 27;328(21):1521-7. doi: 10.1056/NEJM199305273282103.
Results Reference
background

Learn more about this trial

A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

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